Peptidase inhibitor 16 promotes proliferation of pancreatic ductal adenocarcinoma cells through OASL signaling.

Pancreatic ductal adenocarcinoma (PDAC) is a highly invasive cancer with a poor prognosis and a 5-year survival rate of less than 11%. As a member of the CAP superfamily of proteins, the role of peptidase inhibitor 16 (Pi16) in tumor progression is still unclear. Immunohistochemistry and quantitative RT-PCR methods were used to detect the expression levels of Pi16 protein and mRNA in PDAC patients. CRISPR/Cas9 technology was used to knock out the expression of Pi16 in PDAC cell lines. In vivo and in vitro experiments were used to verify the effect of Pi16 on PDAC proliferation ability. By RNA sequencing, we found that oligoadenylate synthetase L (OASL) can serve as a potential downstream target of Pi16. The expression of Pi16 was higher in PDAC tissues than in matched adjacent tissues. High expression of Pi16 was associated with PDAC progression and poor prognosis. Overexpression of Pi16 could promote the proliferation of PDAC cells in vitro and in vivo. Bioinformatics analysis and coimmunoprecipitation assays showed that Pi16 could bind to OASL. Moreover, the functional recovery test confirmed that Pi16 could promote the proliferation of PDAC via OASL. Our present study demonstrates that Pi16 might participate in the occurrence and development of PDAC by regulating cell proliferation by binding to OASL, indicating that Pi16 might be a promising novel therapeutic target for PDAC.

Comparison between 68Ga-PSMA-11 PET/CT and multiparametric magnetic resonance imaging in patients with biochemically recurrent prostate cancer following robot-assisted radical prostatectomy.

BACKGROUND/PURPOSE: We sought to compare the diagnostic performances of 68Ga-PSMA-11 PET/CT and prostate/whole-abdomen multiparametric magnetic resonance imaging (PWAmpMRI) in Taiwanese patients with biochemically recurrent prostate cancer following robot-assisted radical prostatectomy. METHODS: Between June 2017 and December 2018, we prospectively enrolled 34 patients. Upon review of all available clinical and imaging data, a best valuable comparator (BVC) was defined on an individual basis in the light of a consensus reached by a multidisciplinary tumor board. Diagnostic positivity was investigated in relation to the different lesion types. RESULTS: On a patient-based analysis, 68Ga-PSMA-11 PET/CT and PWAmpMRI showed a moderate agreement (kappa coefficient = 0.62). 68Ga-PSMA-11 PET/CT identified local recurrences, regional, and non-regional lymph node metastases, and bone metastases in 15, 10, 1, and 5 patients, respectively. Conversely, PWAmpMRI detected these lesions in 26, 8, 1, and 4 patients, respectively. When the BVC was used as reference standard, the positive diagnostic rates for local recurrences, regional lymph node metastases, non-regional lymph node metastases, and bone metastases were 57.7%, 90.9%, 100%, and 100%, respectively for 68Ga-PSMA-11 PET/CT, and 100%, 72.7%, 100%, and 80% for PWAmpMRI, respectively. The use of both PWAmpMRI and 68Ga-PSMA-11 PET/CT showed a complete diagnostic yield for detecting both local recurrence and systemic failure when PSA levels reached 0.5 ng/mL. CONCLUSION: Due to urine radioactivity, 68Ga-PSMA-11 PET/CT performs less than PWAmpMRI on local recurrences. However, it can have a complementary diagnostic role in the detection of lymph node metastases and in identifying non-axial bone metastases beyond the PWAmpMRI scanning field.

Management and clinical outcomes of patients with recurrent/progressive ovarian clear cell carcinoma.

BACKGROUND/PURPOSE: Ovarian clear cell carcinoma (OCCC) with recurrence/progression after treatment has dismal prognosis. We aimed to investigate the management and outcomes of such patients. METHODS: OCCC patients who were treated between 2000 and 2013 with cancer recurrence or progression after primary treatment were analyzed. Univariate and multivariate analyses were used to identify the independent predictors of survival after recurrence (SAR) and cancer-specific survival (CSS). RESULTS: A total of 64 patients experienced treatment failure (49 recurred after remission and 15 progressed without remission). The 5-year CSS rates of recurrent/progressive OCCC patients were 22.9% (progression group: median CSS 5.9 months [range, 0.8-25.2] vs recurrence group: 43.6 months [range, 7.1-217.8]; p < 0.001). Patients with solitary recurrence had significantly better SAR than those with disseminated relapse (median: not reached vs 10.4 months, p < 0.001). On multivariate analysis, six models each for SAR and CSS were formulated alternatively including highly correlated variables for the recurrence group. Of these models, solitary relapse pattern (HR: 0.07, p < 0.001), progression-free interval (PFI) > 12 months (HR: 0.22-0.40, p = 0.001 and p = 0.023), CA125 < 35 U/mL at initial recurrence (HR: 0.32, p = 0.007), and overall salvage treatment including radiotherapy (HR: 0.19, p = 0.001) were significant predictors of favorable SAR. The same significant predictors were selected for CSS. CONCLUSION: Recurrent OCCC can be treated with curative intent if the relapse is solitary and can be completely resected or encompassed with radiotherapy, whereas novel therapies are needed for disseminated relapse or progression during primary treatment.

Prognostic model based on magnetic resonance imaging, whole-tumour apparent diffusion coefficient values and HPV genotyping for stage IB-IV cervical cancer patients following chemoradiotherapy.

OBJECTIVES: To develop and validate a prognostic model of integrating whole-tumour apparent diffusion coefficient (ADC) from pretreatment diffusion-weighted (DW) magnetic resonance (MR) imaging with human papillomavirus (HPV) genotyping in predicting the overall survival (OS) and disease-free survival (DFS) for women with stage IB-IV cervical cancer following concurrent chemoradiotherapy (CCRT). METHODS: We retrospectively analysed three prospectively collected cohorts comprising 300 patients with stage IB-IV cervical cancer treated with CCRT in 2007-2014 and filtered 134 female patients who underwent MR imaging at 3.0 T for final analysis (age, 24-92 years; median, 54 years). Univariate and multivariate Cox regression analyses were used to evaluate the whole-tumour ADC histogram parameters, HPV genotyping and relevant clinical variables in predicting OS and DFS. The dataset was randomly split into training (n = 88) and testing (n = 46) datasets for construction and independent bootstrap validation of the models. RESULTS: The median follow-up time for surviving patients was 69 months (range, 9-126 months). Non-squamous cell type, ADC10 <0.77 × 10-3 mm2/s, T3-4, M1 stage and high-risk HPV status were selected to generate a model, in which the OS and DFS for the low, intermediate and high-risk groups were significantly stratified (p < 0.0001). The prognostic model improved the prediction significantly compared with the International Federation of Gynaecology and Obstetrics (FIGO) stage for both the training and independent testing datasets (p < 0.0001). CONCLUSIONS: The prognostic model based on integrated clinical and imaging data could be a useful clinical biomarker to predict OS and DFS in patients with stage IB-IV cervical cancer treated with CCRT. KEY POINTS: • ADC 10 is the best prognostic factor among ADC parameters in cervical cancer treated with CCRT • A novel prognostic model was built based on histology, ADC 10 , T and M stage and HPV status • The prognostic model outperforms FIGO stage in the survival prediction.

Roles of posttherapy 18F-FDG PET/CT in patients with advanced squamous cell carcinoma of the uterine cervix receiving concurrent chemoradiotherapy.

PURPOSE: To assess the clinical roles of [18F]fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) performed 2-3 months after completion of concurrent chemoradiotherapy (CCRT), along with pretherapy characteristics, in patients with advanced squamous cell carcinoma of the uterine cervix enrolled in a prospective randomized clinical trial. METHODS: Posttherapy PET/CT in patients with advanced FIGO stage or positive pelvic or para-aortic lymph node (PALN) defined on pretherapy PET/CT was classified as positive, equivocal, or negative. Overall survival (OS) rates between patients with different PET/CT results are compared. Pretherapy characteristics are examined for association with posttherapy PET/CT results and for prognostic significance in patients with equivocal or negative PET/CT. RESULTS: PET/CT scans (n = 55) were positive, equivocal and negative in 9, 13 and 33 patients, respectively. All patients with positive scans were confirmed to have residual or metastatic disease and died despite salvage therapies. There is a significant OS difference between patients with positive and equivocal scans (P < .001) but not between patients with equivocal and negative scans (P = .411). Positive pretherapy PALN is associated with positive posttherapy PET/CT (P = .033) and predicts a poorer survival in patients with equivocal or negative posttherapy PET/CT (P < .001). CONCLUSIONS: Positive PET/CT 2-3 months posttherapy implies treatment failure and novel therapy is necessary to improve outcomes for such patients. A more intense posttherapy surveillance may be warranted in patients with positive pretherapy PALN.

Comparison of positron emission tomography/computed tomography and magnetic resonance imaging for posttherapy evaluation in patients with advanced cervical cancer receiving definitive concurrent chemoradiotherapy.

PURPOSE: Our purpose was to assess the diagnostic performance of positron emission tomography/computed tomography (PET/CT) and pelvic/abdominal magnetic resonance imaging (MRI) after concurrent chemoradiotherapy (CCRT) for posttherapy evaluation in patients with advanced cervical cancer. METHODS: Patients with cervical squamous cell carcinoma, either with advanced FIGO stage or with positive pelvic or para-aortic lymph node (PALN), received PET/CT using [18F]fluorodeoxyglucose and MRI including diffusion-weighted imaging between 2 and 3 months after CCRT completion. PET/CT were interpreted independently by two nuclear medicine physicians and MRI by two radiologists using the same scoring system. Active residual tumor was proven by pathological confirmation or disease progression on imaging studies within one year after CCRT and the disease regions were classified as local, regional, PALN, or distant. Patient-based and region-based comparison was performed using the receiver operating characteristic curve analysis. RESULTS: The study included 55 patients and 15 (27%) patients had active residual tumor. The diagnostic performance of PET/CT is significantly superior to that of MRI in patient-based analysis (P = 0.025) and in the detection of local (P = 0.045) and regional (P = 0.014) disease. The patient-based sensitivity, specificity, and accuracy of PET/CT are 60%, 100%, and 89% while those of MRI are 27%, 100%, and 80%. CONCLUSIONS: PET/CT is superior to MRI for posttherapy evaluation in patients with advanced cervical cancer 2-3 months after definitive CCRT, mainly for the detection of residual local and regional disease. Patients with negative or equivocal results should be followed up regularly due to suboptimal sensitivities of imaging.

Positron emission tomography in the management of documented or suspected recurrent ovarian cancer.

BACKGROUND: To prospectively evaluate the value of positron emission tomography (PET) or integrated computed tomography (CT) and PET (PET/CT) in the management of documented or suspected recurrent ovarian cancer. METHODS: Patients with ovarian cancer who had completed primary cytoreductive surgery and standard adjuvant chemotherapy were studied to evaluate the following indications: (1) CA125 elevation after complete remission with negative CT or magnetic resonance imaging (MRI) result; (2) post-therapy surveillance CT/MRI-detected suspicious lesions that guided biopsy was not feasible; (3) documented relapse for restaging prior to or after curative salvage therapy. The clinical impact of PET, as compared with those of CT/MRI, was determined on a per scan basis. RESULTS: From 2002 to 2009, 73 patients were recruited, and 92 PET scans were performed. Up to June 2015, 53 patients had died of disease, four were alive with disease, and the remaining 16 were alive without disease. Among the 92 scans, PET had positive impacts in 72.8%, no clinical impacts in 21.7%, and negative impacts in 5.4%. For indication 1, the sensitivity and positive predictive value of PET in detecting recurrence were 80.0% and 92.3%, respectively. For indication 2, the sensitivity, specificity, positive predictive value, and negative predictive value of PET were 91.2%, 62.5%, 91.2%, and 62.5%, respectively. For indication 3, PET provided positive impact in 85.3% and negative impact in 2.9% of the 34 scans. CONCLUSION: PET has value in the management of suspected or documented recurrent ovarian cancer, with positive impacts on confirming recurrent status and offering a better treatment plan.

(18)F-FDG PET in small-cell cervical cancer: a prospective study with long-term follow-up.

PURPOSE: Small-cell cervical cancer (SCCC) is rare and prone to metastasize. We conducted a prospective study to evaluate the role of (18)F-FDG PET in the management of this aggressive malignancy. METHODS: Patients with untreated primary, histologically confirmed SCCC were enrolled. (18)F-FDG PET (or PET/CT) was performed immediately after MRI or CT, for primary staging, monitoring response to treatment or restaging when there was suspicion of recurrence. The clinical impact of PET was determined on a scan basis. RESULTS: A total of 25 patients were recruited and 43 PET scans were performed. The PET images were obtained for primary staging (25 patients), monitoring response (10 patients) and restaging when there was suspicion of recurrence (8 patients). The median follow-up time in event-free patients was 109.3 months (range 97.5 - 157.7 months). A positive impact of PET was found in 8 (18.6 %) of the 43 scans, which included detection of additional regions of distal lymph node (LN) metastasis (one primary staging scan, two restaging scans), bone metastasis (two primary staging scans, one monitoring response scan), and exclusion of false-positive lesions on MRI (one primary staging scan, one restaging scan). On the other hand, one negative impact was recorded as one false-positive lesion on a restaging PET scan. One positive impact was noted for monitoring response (bone metastasis). The impact of three scans was indeterminate. The positive impact of down-staging in avoiding overtreatment but finding additional distal LN (except one on restaging) or bone metastases had no beneficial effect on long-term survival. CONCLUSION: The results of this preliminary study suggest that PET is useful in the management of SCCC. PET could have more value in detecting occult metastases if future novel therapies are able to offer better control of extensive SCCC.

Utility of (18)F-FDG PET/CT in patients with advanced squamous cell carcinoma of the uterine cervix receiving concurrent chemoradiotherapy: a parallel study of a prospective randomized trial.

PURPOSE: The aim of this prospective study was to assess the usefulness of (18)F-FDG PET/CT performed before and during treatment for predicting treatment failure in patients with advanced squamous cell carcinoma of the uterine cervix treated with concurrent chemoradiotherapy (CCRT). METHODS: Patients with cervical squamous cell carcinoma, International Federation of Gynecology and Obstetrics stage III/IVA or positive pelvic or paraaortic lymph node (LN) metastasis without other distant metastasis on PET/CT entering a randomized trial of CCRT (AGOG 09-001) were eligible. PET/CT scans were performed at baseline, during week 3 of CCRT and 2 - 3 months after CCRT. PET/CT parameters were correlated with sites of failure and overall survival (OS). The resulting predictors developed from the study cohort were validated on two independent datasets using area under the curve values, sensitivities and specificities. RESULTS: With a median follow-up of 54 months for survivors, 20 (36 %) of the 55 eligible patients were proven to have treatment failure. Sites of failure were local in five, regional in 11, and distant in 11. Four predictors for local failure, three for regional failure, and four for distant failures were identified. After validation with two independent cohorts of 31 and 105 patients, we consider the following as clinically useful predictors: pretreatment metabolic tumour volume (MTV) and during-treatment cervical tumour MTV for local failure; during-treatment SUVnode (maximum standardized uptake value of LNs) for regional and distant failure, and during-treatment MTV for distant failure. During-treatment SUVnode (P = .001) and cervical tumour MTVratio (P = .004) were independent significant predictors of OS by stepwise Cox regression. CONCLUSION: PET/CT imaging before and during treatment is useful for predicting failure sites and OS, making tailored therapeutic modifications feasible with potential outcome improvement during primary therapy.

A randomized trial comparing concurrent chemoradiotherapy with single-agent cisplatin versus cisplatin plus gemcitabine in patients with advanced cervical cancer: An Asian Gynecologic Oncology Group study.

OBJECTIVE: A recent randomized trial demonstrated that concurrent chemoradiotherapy (CCRT) with weekly cisplatin and gemcitabine, followed by two adjuvant cycles of cisplatin and gemcitabine improved survival for advanced cervical cancer patients. An Asian Gynecologic Oncology Group (AGOG) study was designed to determine whether only adding gemcitabine in the chemoradiation phase without adjuvant chemotherapy could improve survival. METHODS: Between March 2009 and March 2013, 74 eligible patients with International Federation of Obstetrics and Gynecology stage III/IVA cervical cancer or stage I/II with positive pelvic/para-aortic nodal metastasis were enrolled. Thirty-seven patients were randomized to arm C (weekly cisplatin 40mg/m(2)) and 37 patients were randomized to arm CG (weekly cisplatin 40mg/m(2) and gemcitabine 125mg/m(2)), for six cycles. Six eligible patients were excluded before the beginning of treatment. RESULTS: An interim analysis showed superimposable progression-free (PFS) and overall survival (OS), a decision of closing accrual was made. A 3-year PFS was similar in both arms (arm C 65.1% vs. arm CG 71.0%, p=0.71), and a 3-year OS was 74.1% in arm C vs. 85.9% in arm CG (p=0.89), but crossed over at 5years. Grade 2-4 hematological toxicities, including neutropenia (p=0.028) and thrombocytopenia (p=0.001), were more frequent in arm CG than arm C. CONCLUSIONS: Despite limitation in power, it suggests that only adding gemcitabine at the CCRT phase does not provide substantially superior results, but treatment toxicities could increase. Further studies are required to determine the role of post-CCRT adjuvant chemotherapy in advanced cervical cancer.

Computed tomography, magnetic resonance imaging and FDG positron emission tomography in the management of vulvar malignancies.

OBJECTIVES: To prospectively evaluate the value of CT or MRI (CT/MRI) and PET in the management of vulvar malignancies. METHODS: Abdominal and pelvic CT/MRI and whole-body (18) F-FDG (fluorodeoxyglucose) PET or PET/CT (collectively designated PET hereafter) were performed. Lesion status was determined by the pathological findings or clinical follow-up. The diagnostic efficacy was evaluated by receiver operating characteristic (ROC) curve analysis. The clinical impact of PET was determined on a per scan basis. RESULTS: Twenty-three patients were enrolled, and 38 PET examinations were performed. CT/MRI and PET studies were used for primary staging (n = 17), monitoring the response (n = 7) and restaging after recurrence (n = 14). In primary staging, there was no significant difference between CT/MRI and PET in detecting metastatic inguinal lymph nodes (ILN). CT/MRI was significantly more efficacious than PET in detecting pelvic lymph node (PLN) or distant metastasis (p = 0.007 by ROC per patient basis). PET findings resulted in two positive impacts and one negative impact for both primary staging and restaging. CONCLUSIONS: False-positive PLN or distant metastasis PET findings are not uncommon, and hence should be interpreted with caution. PET can be supportive when metastatic ILN/PLN or distant metastasis is suspected on CT/MRI. KEY POINTS: • False-positive metastatic PLN or distant metastasis PET findings are not uncommon. • CT/MRI has value in the management of vulvar malignancies. • PET can be supportive when metastasis is suspected by CT/MRI.

Molecular imaging in the management of gynecologic malignancies.

OBJECTIVES: The purpose of this review is to summarize literature pertaining to clinical roles of positron emission tomography (PET) or integrated PET and computed tomography (PET/CT) scans, magnetic resonance imaging (MRI) and emerging techniques of these two molecular imaging tools for gynecologic malignancies. METHODS: PubMed and MEDLINE databases search for articles published before June 2014 was performed. Only English-language articles were considered. Search terms included "cervical cancer", "endometrial cancer", "uterine cancer", "uterine sarcoma", "ovarian cancer" and "vulvar cancer", in association with "FDG", "PET", "PET/CT", "MRI", "PET/MR", "diffusion", "spectroscopy" and "clinical trial". RESULTS: Topics explored included PET, PET/CT and MRI for diagnosis of malignancy, prognostic implications, clinical staging of disease extent, monitoring treatment response, post-therapy surveillance, diagnosis of treatment failure and restaging, and follow-up after salvage therapy in gynecologic malignancies. CONCLUSIONS: Molecular imaging (mainly PET and MRI) plays important roles in the management of gynecologic malignancies. Molecular imaging has various impacts in different clinical scenarios. Emerging technologies will continuously improve our practice. Prospective studies with defined endpoints are necessary to evaluate roles of these novel tools in management of gynecologic malignancies.

Treatment failure in endometrial carcinoma.

OBJECTIVE: Our aim was to investigate the outcomes and prognostic factors after treatment failure of endometrial cancer. METHODS: A total of 923 endometrial cancer patients were treated between 2000 and 2010, of which 109 experienced treatment failure. Treatment failure was defined as relapse after complete removal of all cancerous lesions or persistent/progressive disease despite treatment. Variables including clinicopathological features at initial treatment, type of primary treatment, failure pattern, salvage treatment, and outcomes were analyzed. Kaplan-Meier survival curves were compared with log-rank test. Cox proportional hazards regression model was used to identify significant prognostic factors. RESULTS: Eighteen cases with persistent/progressive disease died shortly from primary diagnosis (1-23 months). The remaining 91 patients had recurrences in vagina only (8.8%), pelvis (3.3%), distant (63.7%), and combined pelvic-distant sites (24.2%). Median time to recurrence was 13.3 months (3.2-97.2 months). The median follow-up after recurrence of survivors was 60.5 months (10.6-121.7 months). The median survival after recurrence (SAR) was 20.3 months (1.9-121.7 months) with 5-year SAR rate of 32.4%. By multivariate analysis, initial stage II to IV (hazards ratio [HR], 3.41; 1.53-7.60; P = 0.003), type II histology (HR, 2.50; 1.28-4.90; P = 0.008), positive peritoneal cytology (HR, 2.23; 1.07-4.68; P = 0.033), and recurrence at multiple sites (HR, 2.51; 1.30-4.84; P = 0.006) were significantly associated with poor SAR. The 5-year SAR rates in patients with solitary vaginal, nodal/liver, or pulmonary/bony recurrence were 83.3%, 50.5%, and 24.2%, respectively. Ten cases with resectable or irradiatable recurrence at multiple sites or multiple relapses attained SAR greater than 5 years after multimodality salvage therapy. CONCLUSIONS: Initial stage II to IV, type 2 histology, positive cytology, and recurrence at multiple sites were significant poor prognostic factors. Curative intent salvage therapy remains a viable option for cases with resectable or irradiatable multiple recurrences and solitary distant metastasis.

The application of machine learning on brain imaging features of different narcolepsy subtypes.

STUDY OBJECTIVES: Narcolepsy is a central hypersomnia disorder, and differential diagnoses between its subtypes can be difficult. Hence, we applied machine learning to analyze the positron emission tomography (PET) data of patients with type 1 or type 2 narcolepsy, and patients with type 1 narcolepsy and comorbid schizophrenia, to construct predictive models to facilitate the diagnosis. METHODS: This is a retrospective and prospective case-control study of adolescent and young adult patients with type 1 or type 2 narcolepsy, and type 1 narcolepsy and comorbid schizophrenia. All participants received 18-F-fluorodeoxy glucose PET, sleep studies, neurocognitive tests, sleep questionnaires, and human leukocyte antigen typing. The collected PET data were analyzed by feature selections and classification methods in machine learning to construct predictive models. RESULTS: A total of 314 participants with narcolepsy were enrolled; 204 had type 1 narcolepsy, 90 had type 2 narcolepsy, and 20 had type 1 narcolepsy and comorbid schizophrenia. We used three filter methods for feature selection followed by a comparative analysis of classification methods. To apply a small number of regions of interest (ROI) and high classification accuracy, the Naïve Bayes classifier with the Term Variance as feature selection achieved the goal with only three ROIs (left basal ganglia, left Heschl, and left striatum) and produced an accuracy of higher than 99%. CONCLUSIONS: The accuracy of our predictive model of PET data are promising and can aid clinicians in the diagnosis of narcolepsy subtypes. Future research with a larger sample size could further refine the predictive model of narcolepsy.

Clinical factor-based risk stratification for precision therapy in locally advanced squamous cell carcinoma of the uterine cervix.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard of care for locally advanced cervical cancer. In this study, we analyzed the pretreatment clinical and 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) characteristics of patients with locally advanced cervical squamous cell carcinoma (SCC) to develop a scoring prototype for risk stratification. METHODS: Two cohorts were constructed in this study. Cohort 1 comprised patients with cervical SCC with 2009 FIGO stage III-IVA or stage I-II with positive pelvic or para-aortic lymph node (PALN) on PET/CT from AGOG09-001 trial. Cohort 2 comprised patients with similar characteristics who had received adequate therapy in our hospital between 2016 and 2021. Pretreatment patient characteristics and PET/CT parameters including maximum standardized uptake value (SUVmax ) and metabolic tumor volume (MTV) of primary tumor and nodal SUVmax were assessed for cancer-specific survival (CSS) using multivariate Cox regression. RESULTS: Analysis of combined data from cohorts 1 (n = 55) and 2 (n = 128) indicated age ≥ 66 years, primary tumor MTV ≥87 mL, and positive PALN on PET/CT to be independently significant adverse predictors for CSS (p < 0.001, p = 0.014, and p = 0.026, respectively) with a median follow-up duration of 51 months. Assigning a score of 1 to each adverse predictor, patients with cumulative risk scores of 0, 1, 2, and 3 were discovered to have a 5-year CSS of 86.9%, 71.0%, 32.2%, and 0%, respectively (p < 0.001). CONCLUSION: Age, primary tumor MTV, and positive PALN on PET/CT may serve as independent predictors of poor survival in patients with locally advanced cervical SCC. Our findings indicate that patients without any adverse factors can receive standard CCRT, whereas those with at least one adverse factor can consider novel combination therapies or clinical trials.

Personalized neoantigen-based T cell therapy triggers cytotoxic lymphocytes expressing polyclonal TCR against metastatic ovarian cancer.

Neoantigen-reactive cytotoxic T lymphocytes play a vital role in precise cancer cell elimination. In this study, we demonstrate the effectiveness of personalized neoantigen-based T cell therapy in inducing tumor regression in two patients suffering from heavily-burdened metastatic ovarian cancer. Our approach involved the development of a robust pipeline for ex vivo expansion of neoantigen-reactive T lymphocytes. Neoantigen peptides were designed and synthesized based on the somatic mutations of the tumors and their predicted HLA binding affinities. These peptides were then presented to T lymphocytes through co-culture with neoantigen-loaded dendritic cells for ex vivo expansion. Subsequent to cell therapy, both patients exhibited significant reductions in tumor marker levels and experienced substantial tumor regression. One patient achieved repeated cancer regression through infusions of T cell products generated from newly identified neoantigens. Transcriptomic analyses revealed a remarkable increase in neoantigen-reactive cytotoxic lymphocytes in the peripheral blood of the patients following cell therapy. These cytotoxic T lymphocytes expressed polyclonal T cell receptors (TCR) against neoantigens, along with abundant cytotoxic proteins and pro-inflammatory cytokines. The efficacy of neoantigen targeting was significantly associated with the immunogenicity and TCR polyclonality. Notably, the neoantigen-specific TCR clonotypes persisted in the peripheral blood after cell therapy. Our findings indicate that personalized neoantigen-based T cell therapy triggers cytotoxic lymphocytes expressing polyclonal TCR against ovarian cancer, suggesting its promising potential in cancer immunotherapy.

Metabolic tumor volume by 18F-FDG PET/CT is prognostic for stage IVB endometrial carcinoma.

OBJECTIVE: The objective of this study was to evaluate the potential prognostic factors in patients with primary stage IVB endometrial carcinoma, incorporating parameters from (18)F-FDG PET/CT such as standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). METHODS: Patients with primary M1 endometrial carcinoma who received (18)F-FDG PET/CT before treatment were retrospectively analyzed. Histological type, histological grade, T stage, N stage, age, ECOG performance status, hormone receptor status, metastatic patterns, number of involved metastatic patterns, serum CA125 level, and (18)F-FDG PET/CT derived parameters including total body SUVmax, total body MTV, and total body TLG were considered as potential prognostic factors for overall survival. Cox proportional hazards regression model was used for statistical analysis. RESULTS: Fifteen patients were eligible with a median survival of 17 months. Total body MTV and total body TLG were highly collinear (Pearson's r=0.978) and were found to be significant prognosticators (P=0.010 and 0.011 respectively). Four patients with total body MTV above 450 mL (or total body TLG above 2700 g) had a median survival of two months, while the remaining patients had a median survival of 47 months. CONCLUSION: Total body MTV is a significant prognostic factor for overall survival in patients with stage IVB endometrial carcinoma. Patients with total body MTV above 450 mL had a very poor survival, while more aggressive therapy may be considered in the remaining patients in pursuit of prolonged survival.

Prostate-specific membrane antigen (PSMA) fusion imaging in prostate cancer: PET-CT vs PET-MRI.

OBJECTIVES: To investigate whether PET-CT or PET-MRI is more appropriate for imaging prostate cancer, in terms of primary tumor detection, local staging and recurrence, as well as lymph nodes and distant metastases. METHODS: A systematic literature search was conducted on Embase, PubMed/MEDLINE, and the Cochrane Library database. Studies evaluating the diagnostic performance of PET-CT vs PET-MRI in prostate cancer patients were emphasized. RESULTS: We reviewed 57 original research articles during the period 2016-2021: 14 articles regarding the radiotracer PSMA; 18 articles regarding the primary tumor detection, local tumor staging, managing local recurrence; 17 articles for managing lymph node metastases; and eight articles for managing bone and other distant metastases. PSMA PET could be complementary to mpMRI for primary prostate cancer localization and is particularly valuable for PI-RADS three lesions. PET-MRI is better than PET-CT in local tumor staging due to its specific benefit in predicting extracapsular extension in MRI-occult prostate cancer patients. PET-MRI is likely superior as compared with PET-CT in detecting local recurrence, and has slightly higher detection rates than PET-CT in lymph node recurrence. PET-CT and PET-MRI seem to have equivalent performance in detecting distant bony or visceral metastases. CONCLUSION: In conclusion, PET-MRI is suitable for local and regional disease, either primary staging or restaging, whereas PET-CT is valuable for managing distant bony or visceral metastasis. ADVANCES IN KNOWLEDGE: We reviewed the emerging applications of PET-MRI and PET-CT in clinical aspects. Readers will gain an objective overview on the strength and shortfalls of PET-MRI or PET-CT in the management of prostate cancer.

A case of adult granulosa cell tumor of the ovary with long-term survival after multiple recurrences.

OBJECTIVE: To illustrate the clinical course of a rare case of recurrent adult granulosa cell tumor (AGCT) and discuss the features and management for recurrences. CASE REPORT: A 56-year-old female was first diagnosed with AGCT in 2008 and had uneventful, regular follow-ups until 2013. Recurrence was suspected and proven by computed tomography-guided biopsy. After undergoing complete cytoreductive surgery (CRS) followed by adjuvant megestrol acetate then leuprolide acetate, another recurrence sprouted at the presacral area in 2017. On both occasions, CRS with no visible residual tumor were attained. The patient has remained in complete remission to date with progestin therapy. CONCLUSION: There are currently no standardized tumor markers, imaging exams, or therapies for managing AGCT recurrences. Whole exome sequencing analysis of our patient suggested possible association with triosephosphate isomerase 1 mutation. Regular follow-ups with at least two types of imaging exams and indefinite hormone therapy are crucial for this patient's remission.

Impact of Three-Month Androgen Deprivation Therapy on [68Ga]Ga-PSMA-11 PET/CT Indices in Men with Advanced Prostate Cancer-Results from a Pilot Prospective Study.

Purpose: The purpose of this pilot prospective study is to examine the gallium-68-prostate-specific membrane antigen-11 ([68Ga]Ga-PSMA-11) positron emission tomography/computed tomography (PET/CT) imaging response in patients with advanced or metastatic hormone-naïve prostate cancer (PC) after 3 months of androgen deprivation therapy (ADT). Methods: We prospectively included men with untreated, clinical stage III or IV PC scheduled to receive ADT for at least 6 months. [68Ga]Ga-PSMA-11 PET/CT images were obtained before the start of ADT and 10−14 weeks thereafter. The following indices were examined: maximum standardized uptake value (SUVmax), mean SUV, PSMA total volume, and PSMA total lesion values of the prostate, nodes, bones, and whole-body. The therapeutic response was assessed using the modified PET response criteria in solid tumors 1.0. A subgroup analysis of patients with the International Society of Urological Pathology (ISUP) grade group 5 versus <5 was also performed. Results: A total of 30 patients were eligible. All PSMA PET/CT indices were significantly reduced (p < 0.001) after 3 months of ADT. Twenty-four (80%) patients showed partial response. Complete response, stable disease, and disease progression were observed in two patients each. Sixteen patients with ISUP grade group 5 showed a less prominent SUVmax reduction (p = 0.006), and none of them reached complete response. Conclusions: Three months of ADT in patients with untreated, advanced PC significantly reduced PSMA PET/CT indices. While most participants partially responded to ADT, patients with ISUP grade group 5 showed a less prominent SUVmax reduction. Collectively, our pilot results indicate that [68Ga]Ga-PSMA-11 PET/CT imaging holds promise to monitor treatment response after the first three months of ADT.